Sarcopenia does not impact the outcome of patients with Multiple Mieloma consolidated with autologous Hematopoietic Stem Cell Transplantation.

Sarcopenia has been associated with chronic diseases and cancer. Aim of this study was to evaluate sarcopenia in Multiple Myeloma patients undergoing autologous stem cell trans-plantation. In 68 eligible patients' measurement of skeletal muscle area (cm2) on computed tomography scans at the level of the L3 vertebra (L3-SMI) was performed. 37(54%) patients were categorized as sarcopenic: 26 males with L3-SMI values < 52.4 cm2/m2, and 11 women with L3-SMI values < 38.9 cm2/m2. The majority of sarcopenic patients included were older than 60 years (69%, p=0.0005), and with BMI <25 (75%; p=0.0000). A significant association was found between sarcopenia and Sorror score value > 1 (p=0.02). The Kaplan Meyer curve showed a median OS of 73.5 months for non-sarcopenic patients vs. 86.5 months for sarcopenic patients, suggesting that sarcopenia is not an independent prognostic factor in this cohort of patients.

Protective Effect of Procyanidin-Rich Grape Seed Extract against Gram-Negative Virulence Factors.

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative bacteria. Grape seeds, wine industry by-products, have antioxidant and antimicrobial activity. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera L. cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damage has been studied in a model of Caco-2 cells. The prGSE was characterized at the molecular level using HPLC and NMR. The in vitro activity of prGSE against formation of biofilm of Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli was investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results show that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by the LPS treatment of Caco-2 cells was demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In terms of in vivo activity, an increase in survival of infected G. mellonella larvae after treatment with prGSE was demonstrated. In conclusion, grape seed extracts could be used to reduce GI damage caused by bacterial endotoxin and biofilms of Gram-negative bacteria.

Review Article title: Natural Compounds with Antimicrobial Activities in oral Candida infections during head and neck radiotherapy.

BACKGROUNDS: Oral colonization and infections are frequently observed in patients during and soon after radiation therapy (RT). Infective mucositis is a common side effect associated with cancer therapy, characterized by an inflammation of the oral mucous membranes with histological mucosal and submucosal changes. Ulcerative mucositis is responsible for significant pain, impairing the patient's nutritional intake and leading to local or systemic infections promoting mycosis due to several species of the genus Candida. According to international guidelines, treatment of candidiasis depends on the infection site and patient's condition. SUMMARY: Recently several studies have shown the protective role of natural compounds counteracting the activity of Candida biofilms. The aim of this review is to discuss the antimicrobial activities of natural compounds in fungal infections, especially Candida spp., during and soon after radiotherapy. Indeed new molecules are being discovered and assessed for their capacity to control Candida spp. growth and, probably in the future, will be used to treat oral candidiasis, overall, during radiotherapy. This review reports several preliminary data about preclinical and clinical evidence of their efficacy in the prevention and/or treatment of mucositis due to Radiotherapy with a brief description of the natural compounds with anti-Candida activities. KEY MESSAGES: The increase in the resistance to the available antifungal drugs related to Candida spp. infections increased as well as drug interactions, urging the development of innovative and more effective agents with antifungal action. Recent preclinical and clinical studies are identifying natural substances with anti-inflammatory and antifungal activity that could be tested in the prevention of candidiasis in patients undergoing radiotherapy. Further studies are needed to confirm these preliminary data.

Constipation-Predominant Irritable Bowel Syndrome (IBS-C): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. The pathogenesis of IBS is not completely clear, but it is known to be multifactorial and complex. Endogenous and exogenous factors such as abnormal GI motility, low-grade inflammation, increased epithelial permeability and visceral hypersensitivity, but diet and psychosocial aspects are also recognized as important actors. Furthermore, the interaction between diet and gut microbiota has gained interest as a potential contributor to the pathophysiology of IBS. To date, there is no specific diet for IBS with constipation (IBS-C); however, many studies show that fiber intake, especially soluble fiber such as inulin, could have a positive effect on symptoms. This review aims to evaluate the effects of some nutritional components such as fibers but also functional foods, prebiotics, probiotics and symbiotics on symptoms and microbiota in IBS-C subjects.

Phylogenetic analysis of Prevotella copri from fecal and mucosal microbiota of IBS and IBD patients.

Background: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role. Objectives: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL). Design: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy. Methods: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods. Results: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri. In IBS, a correlation between isolates and disease grading was observed. Conclusion: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases.

Protective Role of Natural Compounds under Radiation-Induced Injury.

In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients' quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.

The Role of Dietary Fibers in the Management of IBD Symptoms.

Inflammatory bowel diseases (IBDs) are chronic, progressive, immune-mediated diseases of the intestinal tract. The main subtypes of IBDs are Chron's disease (CD) and ulcerative colitis (UC). The etiology is still unclear, but there are genetic, environmental and host-related factors that contribute to the development of these diseases. Recent literature has shown that dietary therapy is the cornerstone of IBD treatment in terms of management of symptoms, relapse and care of the pathology. IBD patients show that microbiota dysbiosis and diet, especially dietary fiber, can modulate its composition. These patients are more at risk of energy protein malnutrition than the general population and are deficient in micronutrients. So far, no dietary component is considered responsible for IBD and there is not a specific therapeutic diet for it. The aim of this review is to evaluate the role of dietary fibers in CD and UC and help health professionals in the nutritional management of these pathologies. Further studies are necessary to determine the appropriate amount and type of fiber to suggest in the case of IBD to ameliorate psychosocial conditions and patients' quality of life.

Gut Microbiota and COVID-19: Potential Implications for Disease Severity.

The SARS-CoV-2 pandemic resulted in an unprecedented global crisis. SARS-CoV-2 primarily causes lung infection trough the binding of the virus with the ACE-2 cell receptor located on the surface of the alveolar epithelial cells. Notably, ACE-2 cell receptors are also expressed in the epithelial cells of the intestinal tract (GI). Recent data showed that the microbial communities of the GI might act as local and systematic inflammatory modulators. Gastrointestinal symptoms, including diarrhea, are frequently observed in infected individuals, and recent released data indicate that SARS-CoV-2 may also spread by fecal-oral transmission. Moreover, the gut microbiota's ecosystem can regulate and be regulated by invading pathogens, including viruses, facilitating an effective immune response, which in turn results in less severe diseases. In this regard, increased SARS-CoV-2 mortality and morbidities appear to be frequently observed in elderly immunocompromised patients and in people with essential health problems, such as diabetes, who, indeed, tend to have a less diverse gut microbiota (dysbiosis). Therefore, it is important to understand how the interaction between the gut microbiota and SARS-CoV-2 might shape the intensity of the infection and different clinical outcomes. Here, we provide insights into the current knowledge of dysbiosis during SARS-CoV-2 infection and methods that may be used to re-establish a more correct microbiota composition.

The Origins of NAFLD: The Potential Implication of Intrauterine Life and Early Postnatal Period.

Fetal life and the first few months after birth represent a plastic age, defined as a "window of opportunity", as the organism is particularly susceptible to environmental pressures and has to adapt to environmental conditions. Several perturbations in pregnancy, such as excessive weight gain, obesity, gestational diabetes mellitus and an inadequate or high-fat diet, have been associated with long-term metabolic consequences in offspring, even without affecting birth weight. Moreover, great interest has also been focused on the relationship between the gut microbiome of early infants and health status in later life. Consistently, in various epidemiological studies, a condition of dysbiosis has been associated with an increased inflammatory response and metabolic alterations in the host, with important consequences on the intestinal and systemic health of the unborn child. This review aims to summarize the current knowledge on the origins of NAFLD, with particular attention to the potential implications of intrauterine life and the early postnatal period. Due to the well-known association between gut microbiota and the risk of NAFLD, a specific focus will be devoted to factors affecting early microbiota formation/composition.

Early impairment of food intake in patients newly diagnosed with cancer.

Background: Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis. Patients and methods: Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels. Results: Overall, 102 patients [53 male; median age: 67 (range, 21-88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m2; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy (p = 0.002) and protein intake (p = 0.0257), and greater percentage of weight loss (p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = -0.40; p = 0.01) and protein intake (r = -0.340; p = 0.018). Conclusion: Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed.

Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy.

Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD. Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes. Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath. Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98. Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.

Diarrhea Predominant-Irritable Bowel Syndrome (IBS-D): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms.

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. Gut microbiota, which acts as a real organ with well-defined functions, is in a mutualistic relationship with the host, harvesting additional energy and nutrients from the diet and protecting the host from pathogens; specific alterations in its composition seem to play a crucial role in IBS pathophysiology. It is well known that diet can significantly modulate the intestinal microbiota profile but it is less known how different nutritional approach effective in IBS patients, such as the low-FODMAP diet, could be responsible of intestinal microbiota changes, thus influencing the presence of gastrointestinal (GI) symptoms. The aim of this review was to explore the effects of different nutritional protocols (e.g., traditional nutritional advice, low-FODMAP diet, gluten-free diet, etc.) on IBS-D symptoms and on intestinal microbiota variations in both IBS-D patients and healthy subjects. To date, an ideal nutritional protocol does not exist for IBS-D patients but it seems crucial to consider the effect of the different nutritional approaches on the intestinal microbiota composition to better define an efficient strategy to manage this functional disorder.

The impact of the intestinal microbiota and the mucosal permeability on three different antibiotic drugs.

BackgroundThe totality of bacteria, protozoa, viruses and fungi that lives in the human body is called microbiota. Human microbiota specifically colonizes the skin, the respiratory and urinary tract, the urogenital tract and the gastrointestinal system. This study focuses on the intestinal microbiota to explore the drug-microbiota relationship and, therefore, how the drug bioavailability changes in relation to the microbiota biodiversity to identify more personalized therapies, with the minimum risk of side effects. MethodsTo achieve this goal, we developed a new mathematical model with two compartments, the intestine and the blood, which takes into account the colonic mucosal permeability variation - measured by Ussing chamber system on human colonic mucosal biopsies - and the fecal microbiota composition, determined through microbiota 16S rRNA sequencing analysis. Both of the clinical parameters were evaluated in a group of Irritable Bowel Syndrome patients compared to a group of healthy controls. Key ResultsThe results show that plasma drug concentration increases as bacterial concentration decreases, while it decreases as intestinal length decreases too. ConclusionsThe study provides interesting data since in literature there are not yet mathematical models with these features, in which the importance of intestinal microbiota, the "forgotten organ", is considered both for the subject health state and in the nutrients and drugs metabolism.

Association between Dietary Habits and Fecal Microbiota Composition in Irritable Bowel Syndrome Patients: A Pilot Study.

Intestinal dysbiosis seems to play a role in the pathophysiology of irritable bowel syndrome (IBS). The present pilot study aimed to elucidate the association between nutrient intake and Mediterranean diet (MD) adherence with IBS symptoms and gut microbiota in IBS patients. The nutrient intake of 28 IBS patients and 21 controls was assessed through a food diary, the reference intake ranges (RIs) for energy-yielding macronutrients and the MD serving score (MDSS) index. MD adherence and nutrients intake were compared to IBS symptoms and fecal microbiota, obtained by 16S rRNA targeted-metagenomics. In IBS patients MDSS index was altered compared to controls (p < 0.01). IBS patients with low-MD score reported severe abdominal pain and higher flatulence point-scales. Through Linear discriminant analysis effect size (LEfSe), Erysipelotrichaceae were detected as a microbial biomarker in IBS patients with altered RIs for macronutrients intake, compared to controls. Lactobacillaceae and Lactobacillus were associated to an altered carbohydrates intake in IBS patients, while specific taxonomic biomarkers, such as Aldercreuzia, Mogibacteriaceae, Rikenellaceae, Parabacteroides and F. prausnitzii were associated with an adequate intake of nutrient in these patients. This study supports an association between dietary patterns and gut microbial biomarkers in IBS patients. Further investigations are needed to clarify these connections.

Understanding the relationship between esophageal motor disorders and reflux disease.

INTRODUCTION: The management of gastro-esophageal reflux disease (GERD) patients is often complex as the clinical presentation is heterogeneous and the mechanisms underlying symptoms are multifactorial. In the past decades, investigations conducted with conventional manometry and, above all, the more accurate high resolution manometry (HRM), helped us in exploring the field of esophageal motility and in understanding the link between motor features and GERD pathogenesis. AREAS COVERED: Several studies carried out with conventional manometry and HRM have confirmed a relevant role of esophageal motor function in GERD pathogenesis. In particular, HRM studies have shown a direct correlation between impaired esophageal body motility, disruption of the esophagogastric junction and reflux burden. These findings impact the clinical and therapeutical management of GERD patients. Moreover, HRM findings might be helpful in evaluating patients with proton pump inhibitor (PPI) resistance and inconclusive evidences of GERD. EXPERT OPINION: The relationship between esophageal motility and GERD pathogenesis needs to be further evaluated by multicenter outcome studies involving a large number of GERD patients and healthy controls. However, other more promising areas could be progressed.

Palmitic Acid Affects Intestinal Epithelial Barrier Integrity and Permeability In Vitro.

Palmitic acid (PA), a long-chain saturated fatty acid, might activate innate immune cells. PA plays a role in chronic liver disease, diabetes and Crohn's disease, all of which are associated with impaired intestinal permeability. We investigated the effect of PA, at physiological postprandial intestinal concentrations, on gut epithelium as compared to lipopolysaccharide (LPS) and ethanol, using an in vitro gut model, the human intestinal epithelial cell line Caco-2 grown on transwell inserts. Cytotoxicity and oxidative stress were evaluated; epithelial barrier integrity was investigated by measuring the paracellular flux of fluorescein, and through RT-qPCR and immunofluorescence of tight junction (TJ) and adherens junction (AJ) mRNAs and proteins, respectively. In PA-exposed Caco-2 monolayers, cytotoxicity and oxidative stress were not detected. A significant increase in fluorescein flux was observed in PA-treated monolayers, after 90 min and up to 360 min, whereas with LPS and ethanol, this was only observed at later time-points. Gene expression and immunofluorescence analysis showed TJ and AJ alterations only in PA-exposed monolayers. In conclusion, PA affected intestinal permeability without inducing cytotoxicity or oxidative stress. This effect seemed to be faster and stronger than those with LPS and ethanol. Thus, we hypothesized that PA, besides having an immunomodulatory effect, might play a role in inflammatory and functional intestinal disorders in which the intestinal permeability is altered.

Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults.

In recent years, research has focused on the use of dietary fibers and prebiotics, since many of these polysaccharides can be metabolized by intestinal microbiota, leading to the production of short-chain fatty acids. The metabolites of prebiotic fermentation also show anti-inflammatory and immunomodulatory capabilities, suggesting an interesting role in the treatment of several pathological conditions. Galacto-oligosaccharide and short- and long-chain fructans (Fructo-oligosaccharides and inulin) are the most studied prebiotics, even if other dietary compounds seem to show the same features. There is an increasing interest in dietary strategies to modulate microbiota. The aim of this review is to explore the mechanisms of action of prebiotics and their effects on the principal gastro-intestinal disorders in adults, with a special focus on Galacto-oligosaccharides, Fructo-oligosaccharides, lactulose and new emerging substances which currently have evidence of prebiotics effects, such as xilooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactobionic acid, resistant starch and polyphenols.

Nutritional Aspects in Inflammatory Bowel Diseases.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing, inflammatory disorders of the digestive tract that characteristically develop in adolescence and early adulthood. The reported prevalence of malnutrition in inflammatory bowel disease (IBD) patients ranges between 20% and 85%. Several factors, including reduced oral food intake, malabsorption, chronic blood and proteins loss, and intestinal bacterial overgrowth, contribute to malnutrition in IBD patients. Poor nutritional status, as well as selective malnutrition or sarcopenia, is associated with poor clinical outcomes, response to therapy and, therefore, quality of life. The nutritional assessment should include a dietetic evaluation with the assessment of daily caloric intake and energy expenditure, radiological assessment, and measurement of functional capacity.

Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict PPI response in GERD patients with extra esophageal symptoms.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index are able to increase the diagnostic yield of impedance-pH and are associated to proton pump inhibitor (PPI) response. Few data concerning these variables in patients with extra-esophageal symptoms (EES) are available. AIMS: To evaluate, in EES patients, the role of the conventional and new impedance-pH variables in diagnosing GERD and the predictive value of impedance-pH variables for PPI response. METHODS: Consecutive patients presenting suspected GERD-related EES underwent impedance-pH. Patients treated in the last six months with double dose PPI therapy were enrolled. The presence of concomitant typical symptoms was assessed. RESULTS: 239 EES patients were studied; 102 responders and 137 non-responders. Eighty-one (34%) were affected by non-erosive reflux disease (NERD), 61 (26%) presented reflux hypersensitivity (RH) and 97 (40%) were non-GERD. In NERD and RH groups, a significantly higher proportion of patients with pathological PSPW index or MNBI values compared to non-GERD group was observed. 24 (25%) non-GERD patients presented a pathological PSPW index and/or MNBI. Pathological PSPW index, MNBI and presence of typical symptoms were associated to PPI response. CONCLUSIONS: MNBI and PSPW index measurement increases the diagnostic yield of impedance-pH; abnormal values are associated with a satisfactory response to acid-suppressive therapy in EES patients.